Neurotensin (NT) is a new vasoactive, gut-contracting peptide originally isolated from bovine hypothalami; other interesting biological properties which have been noted include the ability to induce hypotension, hyperglycemia, increased vascular permeability and cyanosis in the rat and to attract human leukocytes in vitro. Using radioimmunoassay we have detected the presence of NT-like substances in extracts of (a) other parts of brain (b) small intestine (c) polymorphonuclear leukocytes and (d) synovial fluid and tissue from arthritic joints. Some of these substances differ from NT chromatographically and immunochemically and yet appear to possess biological activity. We intend to isolate and identify the cross-reacting peptides in (a), (b), and (c) above and to isolate and determine the structure of an immunoreactive fragment of the very large protein in (d) above. Once defined, these structures will be assembled using the Merrifield solid phase procedure and the biological activities of the native and synthetic peptides will be examined and compared to NT. These studies will provide us with necessary information concerning the tissue distribution of NT and may expand our knowledge of the structure(s) and function(s) of this new class of interesting peptide(s).